This proposal describes a series of experiments which will examine will examine how spatial information is processed in the mammalian brain. In previous studies a population of neurons was identified in the postsubiculum (located within the hippocampal formation) which discharge as a function of the animal's head direction, independent of the animal's behavior and spatial location. This spatial signal provides a model system for examining how primary sensory information, entering through various sensory pathways, is transformed into a 'higher level cognitive signal" representing the organism's spatial relationship with its environment. The mechanisms which accomplish this transformation in the central nervous system are not known. The first aim of the proposal is to examine how the head direction cell signal is processed in the brain. To address this issue, three experimental approaches will be pursed. First, the anatomical connectivity of the postsubiculum will be identified using neural anatomical tracing techniques. Second, the electrophysiological properties and spatial sensitivities of single neurons in brain regions projecting to the postsubiculum will be examined. Finally, the processing of head direction cell activity will be monitored in rats in which lesions or chemical treatments have interrupted the circuit. Taken together, the results obtained from these studies will improve our understanding of the neural circuitry involved in the activation of head direction cells. A second line of investigation will focus on how an animal uses the head direction cell signal in behavior and spatial navigation. To date, head direction cell activity has been recorded only in rats moving freely in a cylindrical environment retrieving food pellets. The proposed studies will evaluate how different behavioral paradigms effect head direction cell activity. For example, head direction cell activity will be monitored while an animal performs a classical conditioning or visual discrimination task. Additional experiments will determine whether head direction cell activity can be modified by environmental manipulations. In these experiments, head direction cell activity will be observed as an animal learns its orientation in a novel, or previously familiar environment. Finally, the role of NMDA receptors in establishing an animal's spatial orientation in a novel environment will be explored. The results from the proposed experiments will provide insight into how spatial information is processed in the brain. These findings have implications from human health and behavior. It is common for elderly patients and patients with Alzheimer's disease, a disease often associated with marked pathology of the postsubiculum, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will give us clues about the complex nature of spatial processes in humans.